CN1939319A - Isoglycyrrhiza acid magnesium externally-applied preparation, its making method and usage - Google Patents
Isoglycyrrhiza acid magnesium externally-applied preparation, its making method and usage Download PDFInfo
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Abstract
An exterior-applied magnesium isoglycyrrhetate in the form of ointment, cream, percutaneous paster, film, liniment, etc for treating psoriasis, chronic eczema and dermatitis, contact dermatitis, etc, and its preparing process is also disclosed.
Description
Technical field
The present invention relates to the external preparation of magnesium isoglycyrrhetate, comprise ointment, emulsifiable paste, transdermal patch, membrane, liniment and varnish, also relate to its preparation method and the application on medicine.
Technical background
Glycyrrhizic acid has pharmacological actions such as antiinflammatory, antiallergic action, adjusting immunity, antibiont oxidation and mutation inhibiting.Once used diammonium glycyrrhizinate intravenously administrable treatment psoriasis and dermatitis clinically,, had good efficacy as eczema.The oral formulations of glycyrrhizic acid also be used for clinically treating dermatosis such as psoriasis, eczema as compound glycyrrhizin sheet (trade name beautiful can), but these glycyrrhizic acid preparations all has certain side effect, as water-sodium retention etc., has influenced the compliance of patient's medication.Still do not have glycyrrhizic acid topical application formulation products at present and ask the city.
Chinese patent application CN1381463 " a kind of new chemical compound magnesium isoglycyrrhetate and production method and purposes " discloses magnesium isoglycyrrhetate first, it is a pentacyclic triterpenoid, chemistry 18 α by name, 20 β-carboxyl-11-oxidation-positive oleanane-12-alkene-3 beta-yls-2-O-β-D-glucopyanosyl carboxyl-α-D-Fructus Vitis viniferae pyrans glycosides aldehydic acid magnesium.This magnesium isoglycyrrhetate is the magnesium salt of the optical isomer α body glycyrrhizic acid of natural glycyrrhizic acid, has the animal serum of prevention transaminase and raises, and the effect that alleviates hepatocellular degeneration, necrosis and the cellular infiltration that reduces inflammation can promote liver cell regeneration.Pharmacodynamics and toxicity test prove that its anti-liver injury effect is better than natural glycyrrhizic acid.Magnesium isoglycyrrhetate only has its injection in exploitation at present, is used for the treatment of hepatitis.Application number is that 200410041923.8 Chinese patent application " magnesium isoglycyrrhetate gel and its production and application " discloses the magnesium isoglycyrrhetate gel and can be used for the treatment of abnormality dermatosiss such as eczematous dermatitis.But because gel causes chapped skin easily, we have studied other the external preparation that is suitable for treating psoriasis and dermatitis to be not suitable for plump lichenization such as psoriasis local application, for example ointment, emulsifiable paste, transdermal patch, membrane, liniment and varnish, overcome above-mentioned defective, thereby finished the present invention.
Summary of the invention
The purpose of this invention is to provide several magnesium isoglycyrrhetate external preparation, comprise magnesium isoglycyrrhetate ointment, emulsifiable paste, transdermal patch, membrane, liniment and varnish.
The present invention discloses the preparation method of magnesium isoglycyrrhetate external preparation in addition.
Another purpose of the present invention is open magnesium isoglycyrrhetate external preparation treatment psoriasis, chronic eczema dermatitis, contact dermatitis and the dermopathic purposes of other abnormalitys.
Exterior-applied formulation of the present invention is active component with the magnesium isoglycyrrhetate, and dosage form comprises ointment, emulsifiable paste, transdermal patch, membrane, liniment and/or varnish.
Magnesium isoglycyrrhetate ointment of the present invention and emulsifiable paste contain the magnesium isoglycyrrhetate as active substance, corresponding substrate and pH regulator agent.Wherein ointment base is a water-soluble base.Water-soluble base is a polyethylene glycols, for example: Macrogol 4000, polyethylene glycol 6000, Macrogol 600, PEG400.
Emulsifiable paste matrix is a water-in-oil type, used oil phase is stearic acid, paraffin, Cera Flava, vegetable oil or higher alcohol, the used emulsifying agent of the emulsifiable paste of water-in-oil type is the fatty acid ester or the smooth class of fatty acid Pyrusussuriensis of calcium soap, lanoline, polyhydric alcohol, is preferably sorbester p17, glyceryl monostearate.
Can also according to circumstances add penetrating agent, wetting agent, antiseptic, stabilizing agent in above-mentioned ointment and the emulsifiable paste.
Can also add thickening agent in ointment and the emulsifiable paste, for example Cera Flava, stearic acid, liquid Paraffin, white vaseline.
The magnesium isoglycyrrhetate and the water-soluble base that are added with the pH regulator agent are mixed, stir condensation and just can obtain ointment of the present invention, according to circumstances add penetrating agent, wetting agent, antiseptic, stabilizing agent.If will add wetting agent, pH regulator agent and antiseptic, then preparation method is soluble in water for (1) adds an amount of pH regulator agent with magnesium isoglycyrrhetate, adds wetting agent and antiseptic again.If antiseptic is soluble in the wetting agent, can earlier antiseptic be dissolved in the wetting agent, again with Isoglycyrrhiza acid magnesium solution mixing.(2) it is even that heating in water bath makes the water-soluble base fusion.Then (1) and (2) is mixed, be stirred to condensation, promptly obtain magnesium isoglycyrrhetate ointment.
The preparation process that can enumerate is: 1, magnesium isoglycyrrhetate is added an amount of 10% ammonia and be dissolved in the distilled water, ethyl hydroxybenzoate is dissolved in glycerol, adds the water solublity azone behind the mixing, stirs evenly.2, Macrogol 4000 and PEG400 are mixed,, stir evenly being heated in the water-bath about 70 ℃.3, (1) is added in (2), be stirred to condensation, promptly obtain magnesium isoglycyrrhetate ointment.
The preparation method of emulsifiable paste is, (1) adds an amount of pH regulator agent with magnesium isoglycyrrhetate and is dissolved in distilled water and makes water; (2) oiliness disperse medium, thickening agent and emulsifying agent melting mixing are evenly made oil phase; (3) above-mentioned water is added in the oil phase, under certain bath temperature, be stirred to milky, at room temperature stir condensation again.Add antiseptic when being necessary,, add in water or the oil phase according to the dissolubility of antiseptic.
The preparation process that can enumerate is (1), magnesium isoglycyrrhetate is added an amount of 5% sodium hydroxide is dissolved in the distilled water, adds chlorocresol again to be heated to about 80 ℃ in water-bath, stirs and makes dissolving, is water.(2), be oil phase with Cera Flava, glyceryl monostearate, liquid Paraffin, white vaseline and sorbester p17, put in the evaporating dish, in water-bath, be heated to about 80 ℃, stir evenly.(3), under 80 ℃, water is slowly added in the oil phase, and in water-bath, constantly be stirred to the semi-solid that is creamy white, at room temperature be stirred to nearly condensation again, promptly obtain the magnesium isoglycyrrhetate emulsifiable paste.
Magnesium isoglycyrrhetate transdermal patch of the present invention is made up of backing layer, drug storing layer and protective layer, can increase transdermal speed and effect that release-controlled film and adhered layer are controlled medicine if necessary.
Drug storing layer is made up of active medicine magnesium isoglycyrrhetate, substrate and pH regulator agent, and described substrate is catablasm base material, gel, ointment, emulsifiable paste, solution, suspension or pressure sensitive adhesive (or claiming gluing skeleton).
Described gel is made by hydrophilic macromolecular compounds such as carbomer, polyvinyl alcohol, polyvidone, Polyethylene Glycol, methylcellulose, ethyl cellulose, hydroxyethyl-cellulose, hydroxypropyl cellulose, hypromellose, carboxymethyl cellulose, sodium carboxymethyl cellulose, gelatin or sodium alginate.
Described pressure sensitive adhesive adopts and is made by polyisobutylene, polysiloxanes, acrylate, polyacrylic acid resin, natural rubber.
Described catablasm base material is to be made with cross-linking agent, cross-linking regulator, wetting agent by in hydrophilic macromolecule such as carbomer, polyvinyl alcohol, polyvidone, hypromellose, carboxymethyl cellulose, sodium carboxymethyl cellulose, gelatin, xanthan gum, sodium alginate, polyacrylic acid, the sodium polyacrylate one or more.Wherein cross-linking agent is alumina gel, aluminum sulfate, aluminum acetate, moisture aluminum chloride, aluminum glycinate etc., and cross-linking regulator is citric acid, lactic acid, tartaric acid, gluconic acid, stearic acid, oleic acid, EDTA etc.
Described ointment, emulsifiable paste matrix are ditto described.Described solution or suspension are solvent with water, ethanol, oil.
Described adhered layer is made up of pressure sensitive adhesive or above-mentioned catablasm base material, does not contain medicine or contains the part medicine as loading dose, and the pressure sensitive adhesive that contains the part medicine is also referred to as gluing skeleton.The available pressure-sensitive adhesive material of the present invention has: Polyisobutylene PSA, polysiloxanes pressure sensitive adhesive, acrylate pressure sensitive adhesive, natural rubber or the pressure sensitive adhesive that is made into by polyacrylic resin.
Described drug storing layer and adhered layer can add plasticizer.Plasticizer is selected from paraffin, vaseline, alcohols, long-chain fatty acid phthalate ester, can select one or more chemical compounds wherein for use.
Described release-controlled film is homogeneous membrane or microporous membrane, and available release-controlled film has ethylene-vinyl acetate copolymer film, polysiloxane film, polypropylene screen, cellulose acetate membrane, polychloroethylene film, polyethylene film and polyethylene terephthalate film.
Described backing layer is aluminium foil, polyethylene film, polystyrene film, polychloroethylene film, polypropylene screen, polyester film, polyethylene terephthalate film, aluminum-plastic composite membrane or non-woven fabrics.
The low material of described protective layer usable surface free energy is as the polyethylene film handled through paraffin or Organosilicon Release Agent, polystyrene film, polypropylene screen, polyester film, separate paper etc.
Transdermal patch of the present invention can be made enclosed type, compound membranous type, adhesive matrix type, the cataplasma type of filling.Preferred cataplasma type.Fill the step that case type manufacturing process comprises the preparation drug storing layer, fills drug storing layer and patch molding; The manufacturing process of compound membranous type comprises preparation drug storing layer, adhered layer and protective layer is compound, the step of patch molding; The manufacturing process of adhesive matrix type comprises the step of preparation drug storing layer, patch molding; The manufacturing process of cataplasma type comprises the step of preparation catablasm base material, preparation drug storing layer, patch molding.
Can add penetrating agent, wetting agent, antiseptic, stabilizing agent in the above-mentioned transdermal patch.
Penetrating agent of the present invention can be one or more mixture with any mixed in sulfoxide class, pyrrolones, azone and analog thereof, fatty acid and ester thereof, surfactant, alcohols, polyalcohols, terpenes, amide-type, cyclodextrin, aminoacid and ester thereof, macrocyclic compound, organic acid, the phospholipid etc., one or both mixture with any mixed in preferred alcohol, propylene glycol, azone (Azone), oleic acid, eucalyptus oil, menthol, the Mentholum.
Wetting agent of the present invention is one or more mixture with any mixed in glycerol, propylene glycol, ethylene glycol, Polyethylene Glycol, sorbitol, maltose alcohol, sodium carboxymethyl cellulose, polyvinylpyrrolidone or the hyaluronic acid etc.
In order to improve magnesium isoglycyrrhetate dissolubility in water, add the pH regulator agent, can be triethanolamine, ethylenediamine, lauryl amine, ammonia spirit, sodium bicarbonate, sodium hydroxide or potassium hydroxide etc., preferred ammonia.Control solution pH value is preferably 6.5-8 at 6-9.
Antiseptic of the present invention is one or more mixture with any mixed in ethanol, chlorocresol, thimerosal, sorbic acid, potassium sorbate, benzoic acid, sodium benzoate, chlorobutanol, methyl hydroxybenzoate, ethyl hydroxybenzoate, the propylparaben.
Stabilizing agent of the present invention is a metal-chelator, for example disodium EDTA, EDTA calcium complex disodium salt or diethylenetriamine pentaacetic acid.
The weight of magnesium isoglycyrrhetate accounts for 0.3～20.0% in described ointment, emulsifiable paste, the transdermal patch, preferred 1-10%, the weight of substrate accounts for 0.2～20.0%, the weight of penetrating agent accounts for 0.1～20.0%, the weight of wetting agent accounts for 5.0～40.0%, the weight of antiseptic accounts for 0.1～20.0%, and the weight of stabilizing agent accounts for 0.05～0.20%.
External preparation of the present invention also comprises membrane, liniment or varnish.
Magnesium isoglycyrrhetate and liniment are made up of medicine magnesium isoglycyrrhetate and filmogen.Membrane used film forming material is polyvinyl alcohol, ethylene-vinyl acetate copolymer, acrylic copolymer, cellulose derivative, gelatin, Lac, arabic gum, agar etc., and liniment used film forming material is polyvinyl alcohol, polyvinylpyrrolidone, ethyl cellulose, polyvinyl formal-acetal, polyvinyl butyral resin, collodion etc.
Membrane and liniment can add plasticizer, and used plasticizer is same as above.
Magnesium isoglycyrrhetate varnish of the present invention is made up of medicine magnesium isoglycyrrhetate and disperse medium.Disperse medium has water, ethanol, glycerol, oils and fats etc.Three kinds of solution-type, suspension type and emulsion-types are arranged.Magnesium isoglycyrrhetate solution-type varnish also is added with cosolvent, and used cosolvent is triethanolamine, ethylenediamine, lauryl amine, ammonia spirit, sodium bicarbonate, sodium hydroxide or potassium hydroxide etc.The suspension type varnish also is added with suspending agent, and used suspending agent is glycerol, arabic gum, sodium alginate, agar, cellulose family, carbopol, polyvidone, glucosan, sodium acrylate, silicon Bentonite, thixotrope etc.The emulsion-type varnish comprises oil-in-water type and water-in-oil type, wherein used oil phase is vegetable oil, liquid Paraffin, higher alcohol, dimethyl-silicon wet goods, the used emulsifying agent of oil-in-water type is the derivatives class of soda soap, triethanolamine soap class, fatty alcohol sulphuric acid (ester) sodium class (sodium lauryl sulphate), poly yamanashi esters or polyoxyethylene ether, the same emulsifiable paste of the used emulsifying agent of water-in-oil type.
The inventor has investigated the influence of factors such as light, heat (40 ℃), low temperature to magnesium isoglycyrrhetate external preparation stability of the present invention.The result is that every index there is no significant change, shows that the above quality of the pharmaceutical preparations of the present invention is stable.
Above magnesium isoglycyrrhetate external preparation of the present invention is easy to use, can improve patient's compliance.
Particularly transdermal patch is compared with gel, and cataplasma is pollution clothes not, can take off subsides at any time and use repeatedly, also is easy to control dosage.In addition, cataplasma is compared with the patch of other substrate, with skin the compatibility preferably and affinity is arranged, moisture retention is preferably arranged, easily make keratodermatitis softening, thereby help the absorption of medicine, and there is not pain when peeling off, good permeability, the skin allergy of no rubber cream.
Test below by pharmacological effect exterior-applied formulation of the present invention is described.
1. the influence that medicine of the present invention forms mouse tail scale granular layer
ICR is a mice, body weight 18 ± 2g, ♂ ♀ half and half.Be divided into 4 groups at random, normal control group, ointment group, emulsifiable paste group and transdermal patch group, every group of 10 mices are smeared each medicine at mouse tail respectively, the normal control group is smeared substrate, and the about 0.05ml of consumption smears 1 every day, after smearing 15 days continuously, get rectangularly, use 10% formalin fixed, paraffin embedding apart from the about 2cm of root place tail skin one, HF dyeing, the afterbody scale of each mice of observation under optical microscope.The granular layer cell person that every scale has connection to embark on journey is called the scale that granular layer is arranged.Count the scale number that granular layer is arranged in per 100 scales, statistical procedures is carried out in the t check between administration group and matched group.
Experimental result: three kinds of dosage forms of medicine of the present invention all can significantly improve mouse tail scale granular layer and form number (P＜0.01).Experimental result sees Table 1.
Table 1. medicine of the present invention forms mouse tail scale granular layer to be influenced (x ± s, n=10)
| Group | Granular layer scale ratio (individual/100) is arranged | Rate of change (%) |
| The normal control group | 6.70±1.06 | |
| The ointment group | 10.10±2.81** | 50.75 |
| The emulsifiable paste group | 10.50±3.57** | 56.72 |
| The transdermal patch group | 10.30±2.36** | 53.73 |
*Compare with the normal control group p＜0.01
2. medicine of the present invention is to the splitted influence of mouse vagina epithelial cell
Getting ICR is the ♀ mice, body weight 18 ± 2g, lumbar injection (IP) diethylstilbestrol for three days on end, each 0.2mg was divided into 3 groups, model control group with mice on the 4th day, ointment group and emulsifiable paste group, every group of 10 mices, each administration group is smeared medicine 0.05ml in mouse vagina, and model control group is smeared the substrate of equivalent.Once a day, for three days on end, behind the last medicine one hour, each organized mice IP colchicine 2mg/kg, kill mice behind the 6h, get the vagina specimen with 10% formalin fixed, paraffin embedding, HE dyeing, under optical microscope, count the mitosis number in 300 basal cells, convert out the mitosis number in per 100 basal cells, be referred to as mitotic index.Statistical procedures is carried out in the t check between administration group and matched group.
Experimental result: two kinds of dosage forms of drug ointment of the present invention and emulsifiable paste all can significantly reduce estrogen phase mouse vagina epithelial cell mitotic index (P＜0.01).Result of the test sees Table 2.
Table 2. medicine of the present invention to the splitted influence of mouse vagina epithelial cell (x ± s, n=10)
| Group | The vaginal epithelial cell mitotic index | Rate of change (%) |
| Model control group | 13.30±1.64 | |
| The ointment group | 10.00±1.83** | -24.81 |
| The emulsifiable paste group | 9.90±1.79** | -25.56 |
*Compare with model control group p＜0.01
3. medicine of the present invention is to the influence of contact dermatitis
BALB/C mice, body weight 18 ± 2g.Be divided into 4 groups at random, every group of 10 mices, model control group, ointment group, emulsifiable paste group and transdermal patch group.Each organizes the mouse web portion unhairing, and 150 μ l are coated with abdominal part with 3% azolactone dehydrated alcohol-acetone (3: 1) solution, and in sensitization ear two sides each 0.05ml of coating the previous days two, once a day, continuous 6 days, model control group gave the substrate of equivalent; After the sensitization the 7th day, be coated with two ear two sides with 20 μ l, 1% azolactone olive oil, measure before exciting and excite the thickness of back 24h.
Experimental result: the mice auricle swelling (P＜0.01) that three kinds of remarkable Yi Zhi azolactones of dosage forms energy of medicine of the present invention cause.Result of the test sees Table 3.
Table .3. medicine of the present invention to the influence of mice contact dermatitis (x ± s, n=10)
| Group | Auricle swelling degree μ m | Auricle edema suppression ratio (%) |
| Model control group | 155.20±25.33 | |
| The ointment group | 107.90±18.51 | 30.48 |
| The emulsifiable paste group | 103.00±21.50** | 33.63 |
| The transdermal patch group | 105.30±20.36** | 32.15 |
*Compare with model control group p＜0.01
4. to the effect of mice chronic dermatitis-eczema
The ICR mice, body weight 18 ± 2g is divided into 5 groups at random, every group of 10 mices, normal control group, model control group, ointment group, emulsifiable paste group and transdermal patch group.Each is organized mice and is applied to back sensitization outward with 7%DNCB100 μ l, smears 1%DNCB 5 μ l in the mouse right ear inboard behind the 5d and excites, and excites 1 time every 3d.The administration group is in exciting the back in the inboard coating of mouse right ear, the about 0.05ml of consumption, 2 times/d first.Each is organized in the 4th and excites back 72h to survey the mice ear degree with slide gauge respectively, repeats to survey 3 times at every turn, averages.Each group was got 6 mouse right ears respectively and is done the pathology section after experiment finished, HE dyeing, and calculating corium soaks into the inflammatory cell number.
Experimental result: three kinds of dosage forms of medicine of the present invention can both significantly suppress the mice auricle swelling (P＜0.01) that the DNCB repetitious stimulation causes, reduce the infiltration inflammatory cell number of ear epidermis and corium, alleviate chronic inflammation.Point out three kinds of dosage forms of medicine of the present invention that mice chronic dermatitis-eczema is had significant inhibitory effect.Result of the test sees Table 4,5.
Table .4 medicine of the present invention to the influence of mice chronic dermatitis-eczema (x ± s, n=10)
| Group | Auricle swelling degree μ m | Auricle edema suppression ratio (%) |
| The normal control group | 155.70±24.60** | |
| Model control group | 231.10±34.54 | |
| The ointment group | 181.60±28.06** | 21.42 |
| The emulsifiable paste group | 182.70±25.44** | 20.94 |
| The transdermal patch group | 181.10±18.49** | 21.64 |
*Compare with model control group p＜0.01
Table .5 medicine of the present invention to mouse ear corium soak into number of inflammatory cells (x ± s, n=6)
| Group | Number of inflammatory cells is (individual/mm 2) | Suppression ratio (%) |
| Model control group | 94.83±10.28 | |
| The ointment group | 54.00±9.12** | 43.06 |
| The emulsifiable paste group | 55.50±8.26** | 41.48 |
| The transdermal patch group | 55.83±6.24** | 41.12 |
*Compare with model control group p＜0.01
Pharmacodynamics test shows, three kinds of dosage forms of medicine of the present invention can significantly improve mouse tail scale granular layer and form, significantly suppress estrogen phase mouse vagina epithelial cell mitosis, point out it to have the parakeratosis of correction and antimitotic effect, psoriasis is had the treatment meaning.Three kinds of dosage forms of medicine of the present invention can also significantly alleviate the ear swelling degree of contact dermatitis, chronic dermatitis-eczema mice, alleviate the chronic inflammatory disease performance of animal pattern ear epidermis and corium, reduce and soak into the inflammatory cell number, point out its effect, acute and chronic dermatitis, eczema class dermatosis are had the auxiliary treatment effect with antiinflammatory, anti-allergy action and adjusting body's immunity.
The specific embodiment
Be that the basis describes the present invention in detail below with embodiments of the invention, but the present invention is not limited to this.
Embodiment 1: water-soluble base type ointment
Prescription (200g):
Magnesium isoglycyrrhetate 2g
Macrogol 4000 60g
PEG400 90g
Water solublity azone 4g
Ethyl hydroxybenzoate 0.2g
10% ammonia is an amount of
Glycerol 10g
Distilled water is mended to 200g
Method for making: 1, magnesium isoglycyrrhetate is added an amount of 10% ammonia and be dissolved in the distilled water, ethyl hydroxybenzoate is dissolved in glycerol, adds the water solublity azone behind the mixing, stirs evenly.
2, Macrogol 4000 and PEG400 are mixed,, stir evenly being heated in the water-bath about 70 ℃.
3, (1) is added in (2), moisturizing is stirred to condensation to 200g, promptly.
Embodiment 2: the water-in-oil type emulsifiable paste
Prescription (200g):
Magnesium isoglycyrrhetate 2g
Sorbester p17 4g
Chlorocresol 0.4g
Cera Flava 15g
Liquid Paraffin 50g
White vaseline 10g
Glyceryl monostearate 30g
5% sodium hydroxide is an amount of
Distilled water 88g
Method for making: be oil phase 1,, put in the evaporating dish, be heated in the water-bath about 80 ℃ with Cera Flava, glyceryl monostearate, liquid Paraffin, white vaseline and sorbester p17.
2, magnesium isoglycyrrhetate is added an amount of 5% sodium hydroxide and be dissolved in the distilled water, add chlorocresol,, stir and make dissolving, be water in also being heated in the water-bath about 80 ℃.
3, under about 80 ℃, water is slowly added in the oil phase, and in water-bath, constantly be stirred to the semi-solid that is creamy white, at room temperature be stirred to nearly condensation again, promptly.
Embodiment 3: fill enclosed type magnesium isoglycyrrhetate transdermal patch
The described patch of present embodiment is made up of backing layer, drug storing layer, release-controlled film, adhered layer and protective layer.Each layer material therefor is as follows:
Backing layer: aluminium foil/polyethylene composite film
Protective layer: polyester film
Release-controlled film: ethylene-vinyl acetate copolymer film
Adhered layer: polysiloxanes pressure sensitive adhesive
Drug storing layer (200g):
Magnesium isoglycyrrhetate 20g
Carbomer 4g
Triethanolamine is an amount of
Glycerol 20g
Azone 4g
5% sodium hydroxide is an amount of
Distilled water adds to 200g
Method for making:
1, preparation drug storing layer:
(1) under agitation carbomer is slowly added in the distilled water of amount of preparation 50%, make its abundant swelling.After treating the carbomer complete swelling, add triethanolamine, regulate pH to 7.0, add azone and glycerol then, fully stir.
(2), magnesium isoglycyrrhetate added an amount of 5% sodium hydroxide be dissolved in the distilled water, stir evenly.
(3) (2) are added in (1), fully stir, and adding distil water stir promptly to capacity.
2, fill drug storing layer:
Drug storing layer quantitatively is added between aluminium foil/polyethylene composite film and the ethylene-vinyl acetate copolymer film heat seal sealing by the calibrated shot pump.
3, patch molding:
On polyester film, coat the polysiloxanes pressure sensitive adhesive, compound with (2) again, i.e. molding.
Embodiment 4: compound membranous type magnesium isoglycyrrhetate transdermal patch
The described patch of present embodiment is made up of backing layer, drug storing layer, release-controlled film, adhered layer and protective layer.Each layer material therefor is as follows:
Backing layer: aluminium foil/polyethylene composite film
Protective layer: polystyrene film
Release-controlled film: microporous polypropylene membrane
Adhered layer: Polyisobutylene PSA
Drug storing layer (200g):
Magnesium isoglycyrrhetate 5g
Polyisobutylene PSA 100g
Liquid Paraffin 20g
Azone 8g
5% sodium bicarbonate is an amount of
Dehydrated alcohol 8g
Distilled water adds to 200g
Method for making:
1, preparation drug storing layer:
Magnesium isoglycyrrhetate is added an amount of 5% sodium bicarbonate be dissolved in the distilled water, azone is dissolved in the dehydrated alcohol, mixing both, add liquid Paraffin and Polyisobutylene PSA, fully stir, and adding distil water is mixed well to capacity.Be coated on then on aluminium foil/polyethylene composite film, the thickness of control coating, 60 ℃ of oven dry cover microporous polypropylene membrane the drug storing layer surface then.
2, adhered layer and protective layer are compound:
Polyisobutylene PSA is coated on the polystyrene film 60 ℃ of oven dry.
3, patch molding:
(1) and (2) are compound, cutting, packing, promptly.
Embodiment 5: adhesive matrix type magnesium isoglycyrrhetate transdermal patch
The described patch of present embodiment is made up of backing layer, drug storing layer and protective layer.Each layer material therefor is as follows:
Backing layer: polyester film
Protective layer: separate paper
Drug storing layer (200g):
Magnesium isoglycyrrhetate 2g
Polyacrylate pressure-sensitive 120g
Eucalyptus oil 10g
Dehydrated alcohol adds to 200g
Method for making:
1, preparation drug storing layer:
Magnesium isoglycyrrhetate was pulverized 100 mesh sieves, then itself and eucalyptus oil were added the dehydrated alcohol dispersing and dissolving, added polyacrylate pressure-sensitive again, and weighed after stirring evenly and add dehydrated alcohol, mixed well to capacity, stand-by.
2, patch molding:
Drug storing layer is coated on the polyester film, the thickness of control coating, 60 ℃ of oven dry cover and go up separate paper, cutting, packing, promptly.
Embodiment 6: cataplasma type magnesium isoglycyrrhetate transdermal patch
The described patch of present embodiment is made up of backing layer, drug storing layer and protective layer.Each layer material therefor is as follows:
Backing layer: non-woven fabrics
Protective layer: separate paper
Drug storing layer (200g):
Magnesium isoglycyrrhetate 2g
Carbomer 2g
Sodium polyacrylate 4.8g
Moisture aluminum chloride 0.4g
Citric acid 0.8g
Glycerol 20g
Menthol 8g
5% potassium hydroxide is an amount of
Dehydrated alcohol 10g
Distilled water adds to 200g
Method for making:
1, preparation catablasm base material:
(1) carbomer is dispersed in the distilled water, stirs and make its swelling.
(2) sodium polyacrylate is dispersed in the aqueous solution of glycerol.
(3) citric acid and aluminum chloride are dissolved in distilled water.
(4) (2) are added in (3), stir evenly.Again (1) is added wherein, stir evenly, stand-by.
2, preparation drug storing layer: magnesium isoglycyrrhetate is added an amount of 5% potassium hydroxide be dissolved in the distilled water, menthol is dissolved in the dehydrated alcohol, mixing both, add in the blank catablasm base material, fully stir, and adding distil water stirs promptly to capacity, stand-by.
3, patch molding: above-mentioned drug storing layer is coated on the non-woven fabrics, and the thickness of control coating covers separate paper, cutting, and packing, promptly.
Embodiment 7: the magnesium isoglycyrrhetate membrane
Prescription (200g):
Magnesium isoglycyrrhetate 4g
Polyvinyl alcohol 60g
Glycerol 5g
10% ammonia is an amount of
Distilled water adds to 200g
Method for making: 1, magnesium isoglycyrrhetate is added an amount of 10% ammonia and be dissolved in the distilled water, add glycerol, stir evenly, add polyvinyl alcohol, placement is spent the night.
2, treat the complete moistening expansion of polyvinyl alcohol after, put 65 ℃ of heating in water bath to all dissolvings, ultrasonic degas makes the air ease to the greatest extent, coating materials.
3, coating materials is poured into synthermal glass plate lower edge, promoted coating materials forward with push rod and transfer to thickness 0.07mm, move to baking oven through 70 ℃ of forced air dryings demoulding immediately after 10 minutes, cooling, cutting, packing, promptly.
Embodiment 8: the magnesium isoglycyrrhetate liniment
Prescription (200g):
Magnesium isoglycyrrhetate 2g
Polyvinyl alcohol 8g
Glycerol 20g
Azone 3g
Distilled water 60g
Dehydrated alcohol 105g
Method for making: 1, get polyvinyl alcohol and add in glycerol and the distilled water after the complete moistening expansion, put 65 ℃ of heating in water bath to all dissolvings.
2, get magnesium isoglycyrrhetate and pulverized 100 mesh sieves, add dehydrated alcohol and be uniformly dispersed, add azone, stir evenly.
3, (2) are slowly added in (1), the limit edged stirs, and stirs evenly back packing rapidly, and is airtight, promptly.
Embodiment 9: aqueous solution type magnesium isoglycyrrhetate varnish
Prescription (200g):
Magnesium isoglycyrrhetate 4g
5% sodium bicarbonate is an amount of
Ethyl hydroxybenzoate 0.2g
Distilled water adds to 200g
Method for making: ethyl hydroxybenzoate is added in the distilled water, and the suitably short dissolving of heating adds magnesium isoglycyrrhetate then, adds an amount of 5% sodium bicarbonate after the agitation as appropriate and makes the dissolving clarification, and add distilled water to capacity, stirs evenly, and packing, promptly.
Embodiment 10: suspension type magnesium isoglycyrrhetate varnish
Prescription (200g):
Magnesium isoglycyrrhetate 20g
Hypromellose 2g
Ethyl hydroxybenzoate 0.2g
Glycerol 80g
Distilled water adds to 200g
Method for making: ethyl hydroxybenzoate and hypromellose are added in distilled water and the glycerol, and the suitably short dissolving of heating adds the magnesium isoglycyrrhetate of pulverizing and crossing sieve on the 100th then, weighs after fully stirring and adds distilled water to capacity, stir evenly, and packing, promptly.
Embodiment 11: oil-in-water type magnesium isoglycyrrhetate varnish
Prescription (200g):
Magnesium isoglycyrrhetate 4g
Tween 80 10g
Ethyl hydroxybenzoate 0.2g
Soybean oil 40g
Distilled water adds to 200g
Method for making: 1, magnesium isoglycyrrhetate was pulverized 100 mesh sieves, and mixed with Tween 80, ethyl hydroxybenzoate and distilled water then.
2, pour soybean oil into colloid mill, again (1) is poured into, open colloid mill, until the uniform emulsion of formation, packing, promptly.
Embodiment 12: water-in-oil type magnesium isoglycyrrhetate varnish
Prescription (200g):
Magnesium isoglycyrrhetate 10g
Sorbester p17 6g
Ethyl hydroxybenzoate 0.2g
Soybean oil 120g
10% ammonia is an amount of
Distilled water 63g
Method for making: 1, magnesium isoglycyrrhetate is added an amount of 10% ammonia and be dissolved in the distilled water, add ethyl hydroxybenzoate then, suitably heating makes dissolving, stirs evenly.
2, pour soybean oil and sorbester p17 into colloid mill, again (1) is poured into, open colloid mill, until the uniform emulsion of formation, packing, promptly.
Claims (18)
1, a kind of external preparation that removes gel, wherein active constituents of medicine is a magnesium isoglycyrrhetate.
2, the external preparation of claim 1, wherein the weight of magnesium isoglycyrrhetate accounts for 0.3-20%.
3, the external preparation of claim 2, wherein the weight of magnesium isoglycyrrhetate accounts for 1-10%.
4, the external preparation of claim 1 is ointment, emulsifiable paste, transdermal patch, membrane, liniment or varnish.
5, the external preparation of claim 4 is an ointment, comprises magnesium isoglycyrrhetate, water-soluble base and pH regulator agent.
6, the external preparation of claim 4 is an emulsifiable paste, comprises magnesium isoglycyrrhetate, water-in-oil type substrate and pH regulator agent.
7, the external preparation of claim 4 is a transdermal patch, is made up of backing layer, drug storing layer and protective layer, and wherein drug storing layer is made up of magnesium isoglycyrrhetate, substrate and pH regulator agent.
8, the external preparation of claim 4 is a transdermal patch, is made up of backing layer, drug storing layer, release-controlled film, adhered layer and protective layer, and wherein drug storing layer is made up of magnesium isoglycyrrhetate, substrate and pH regulator agent.
9, the external preparation of claim 8 is a transdermal patch, wherein release-controlled film is homogeneous membrane or microporous membrane, is selected from ethylene-vinyl acetate copolymer film, polysiloxane film, polypropylene screen, cellulose acetate membrane, polychloroethylene film, polyethylene film and polyethylene terephthalate film.
10, the external preparation of claim 8 is a transdermal patch, and wherein adhered layer is made up of pressure sensitive adhesive or catablasm base material, does not contain medicine or contains the part medicine as loading dose.
11, claim 5,6 or 7 external preparation, wherein the pH regulator agent is triethanolamine, ethylenediamine, lauryl amine, ammonia, sodium bicarbonate, sodium hydroxide or potassium hydroxide.
12, the external preparation of claim 8, wherein the pH regulator agent is an ammonia.
13, the external preparation of claim 5, wherein water-soluble base is a polyethylene glycols.
14, the external preparation of claim 6, wherein the substrate oil phase is stearic acid, paraffin, Cera Flava, vegetable oil or higher alcohol.
15, claim 7 or 8 external preparation, its mesostroma is catablasm base material, gel, ointment, emulsifiable paste, solution, suspension, pressure sensitive adhesive.
16, the external preparation of claim 8, its mesostroma are one or more catablasm base materials made with cross-linking agent, cross-linking regulator, wetting agent in carbomer, polyvinyl alcohol, polyvidone, hypromellose, carboxymethyl cellulose, sodium carboxymethyl cellulose, gelatin, xanthan gum, sodium alginate, polyacrylic acid, the sodium polyacrylate.
17, claim 5,6,7 or 8 external preparation also comprise penetrating agent, wetting agent, antiseptic or stabilizing agent.
18, the application of the external preparation of claim 1 in preparation treatment psoriasis, chronic eczema dermatitis, contact dermatitis and other abnormality dermatosis treating medicines.
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| Application Number | Priority Date | Filing Date | Title |
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| CNB2005101061107A CN100544730C (en) | 2005-09-28 | 2005-09-28 | Magnesium isoglycyrrhetate external preparation and its production and application |
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| Application Number | Priority Date | Filing Date | Title |
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| CNB2005101061107A CN100544730C (en) | 2005-09-28 | 2005-09-28 | Magnesium isoglycyrrhetate external preparation and its production and application |
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| Application Number | Title | Priority Date | Filing Date |
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| CN2008101781898A Division CN101422427B (en) | 2005-09-28 | 2005-09-28 | Magnesium isoglycyrrhizinate cream and preparation method and use thereof |
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| CN1939319A true CN1939319A (en) | 2007-04-04 |
| CN100544730C CN100544730C (en) | 2009-09-30 |
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101396368B (en) * | 2007-09-29 | 2010-12-01 | 江苏正大天晴药业股份有限公司 | Use of iso-glycyrrhizic acid and salt thereof in treating allergic rhinitis |
| CN101947322A (en) * | 2010-09-03 | 2011-01-19 | 南方医科大学 | Gel patch matrix and preparation method and application thereof |
| CN101947200A (en) * | 2010-07-30 | 2011-01-19 | 东南大学 | Emulsion type ointment |
| CN103536700A (en) * | 2013-11-12 | 2014-01-29 | 扬州大学 | Chinese medicinal ethosome gel patch for treating herpes zoster and preparation method thereof |
| CN105687125A (en) * | 2016-01-29 | 2016-06-22 | 王绿江 | Silica gel for treating skin diseases |
| CN106177693A (en) * | 2016-09-27 | 2016-12-07 | 泰山医学院 | A kind of Chinese medicine for treating eczema and compound recipe solution thereof |
| CN106309353A (en) * | 2015-06-19 | 2017-01-11 | 江苏吉贝尔药业股份有限公司 | Ointment used for treating psoriasis and preparation method thereof |
| CN108324724A (en) * | 2018-04-10 | 2018-07-27 | 苏州芝宇生物科技有限公司 | The preparation method of a kind of gram of vertical boron sieve dissolvable film preparation and its application |
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2005
- 2005-09-28 CN CNB2005101061107A patent/CN100544730C/en active Active
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101396368B (en) * | 2007-09-29 | 2010-12-01 | 江苏正大天晴药业股份有限公司 | Use of iso-glycyrrhizic acid and salt thereof in treating allergic rhinitis |
| CN101947200A (en) * | 2010-07-30 | 2011-01-19 | 东南大学 | Emulsion type ointment |
| CN101947200B (en) * | 2010-07-30 | 2013-04-03 | 东南大学 | Emulsion type ointment |
| CN101947322A (en) * | 2010-09-03 | 2011-01-19 | 南方医科大学 | Gel patch matrix and preparation method and application thereof |
| CN101947322B (en) * | 2010-09-03 | 2012-07-04 | 南方医科大学 | Gel patch matrix and preparation method and application thereof |
| CN103536700A (en) * | 2013-11-12 | 2014-01-29 | 扬州大学 | Chinese medicinal ethosome gel patch for treating herpes zoster and preparation method thereof |
| CN106309353A (en) * | 2015-06-19 | 2017-01-11 | 江苏吉贝尔药业股份有限公司 | Ointment used for treating psoriasis and preparation method thereof |
| CN105687125A (en) * | 2016-01-29 | 2016-06-22 | 王绿江 | Silica gel for treating skin diseases |
| CN106177693A (en) * | 2016-09-27 | 2016-12-07 | 泰山医学院 | A kind of Chinese medicine for treating eczema and compound recipe solution thereof |
| CN108324724A (en) * | 2018-04-10 | 2018-07-27 | 苏州芝宇生物科技有限公司 | The preparation method of a kind of gram of vertical boron sieve dissolvable film preparation and its application |
Also Published As
| Publication number | Publication date |
|---|---|
| CN100544730C (en) | 2009-09-30 |
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